Four-chamber pacing system for optimizing cardiac output and determining heart condition

ABSTRACT

A pacing system and method for providing multiple chamber pacing of a patient&#39;s heart, and in particular, pacing programmed for treatment of various forms of heart failure. The system utilizes impedance sensing for determining optimum pacing parameters, e.g., for pacing the left ventricle so that left heart output is maximized. The impedance sensing also is used for determination of arrhythmias or progression of heart failure. Impedance sensing is provided for between selected pairs of the four chambers, to enable optimizing of information for control and diagnosis. In a preferred embodiment of the invention, impedance measurements are obtained for determining the timing of right heart valve closure or right ventricular contractions, and the timing of delivery of left ventricular pace pulses is adjusted so as to optimally synchronize left ventricular pacing with the right ventricular contractions. Impedance sensing in the left heart also provides timing of mechanical contraction, and the pacemaker controls pacing to maintain bi-ventricular mechanical synchronization adjusted for maximum cardiac output.

REFERENCE TO PRIORITY APPLICATIONS

This application is a divisional of and claims the benefit of U.S.application Ser. No. 09/799,710, filed Mar 7, 2001, entitled“FOUR-CHAMBER PACING SYSTEM FOR OPTIMIZING CARDIAC OUTPUT ANDDETERMINING HEART CONDITION” to Leinders et al., now abandoned, which isa divisional of and claims, the benefit of U.S. Ser. No. 08/890,427commonly assigned U.S. Pat. No. 6,070,100, filed Dec. 15, 1997, entitled“PACING SYSTEM FOR OPTIMIZING CARDIAC OUTPUT AND DETERMINING HEARTCONDITION” to Bakels et al.

FIELD OF THE INVENTION

This invention relates to cardiac pacing systems and, more particularly,to four-chamber pacing systems with sensors for measuring cardiacmechanical characteristics so as to improve cardiac output forcongestive heart failure and other patients.

BACKGROUND OF THE INVENTION

Congestive heart failure (CHF) is defined generally as the inability ofthe heart to deliver enough blood to the peripheral tissues to meetmetabolic demands. Frequently CHF is manifested by left heartdysfunction, but it can have a variety of sources. For example, CHFpatients may have any one of several different conduction defects. Thenatural electrical activation system through the heart involvessequential events starting with the sino-atrial (SA) node, andcontinuing through the atrial conduction pathways of Bachmann's bundleand internodal tracts at the atrial level, followed by theatrio-ventricular (AV) node, Common Bundle of His, right and left bundlebranches, and final distribution to the distal myocardial terminals viathe Purkinje fiber network. A common type of intra-atrial conductiondefect is known as intra-atrial block (IAB), a condition where theatrial activation is delayed in getting from the right atrium to theleft atrium. In left bundle branch block (LBBB) and right bundle branchblock (RBBB), the activation signals are not conducted in a normalfashion along the right or left bundle branches respectively. Thus, in apatient with bundle branch block, the activation of the ventricle isslowed, and the QRS is seen to widen due to the increased time for theactivation to traverse the conduction path.

CHF manifested by such conduction defects and/or other cardiomyopathiesare the object of considerable research into treatments for improvingcardiac output. For example, drug companies have recognized CHF as amarket opportunity, and are conducting extensive clinical studiesorganized to test the outcome of newly developed drugs in terms ofimproving cardiac performance in these patients. Likewise, it is knowngenerally that four-chamber cardiac pacing is feasible, and can providesignificant improvement for patients having left atrial-ventriculardysfunction, or other forms of cardiac heart failure. While there hasbeen relatively little commercialization of four-chamber pacing, thehypothesis remains that cardiac pump function can clearly be improved bysuch pacing.

The benefits of four-chamber pacing generally have been disclosed andpublished in the literature. Cazeau et al., PACE, Vol. 17, November1994, Part II, pp. 1974-1979, disclose investigations leading to theconclusion that four-chamber pacing is feasible, and that in patientswith evidence of interventricular dyssynchrony, a better mechanicalactivation process can be obtained by resynchronizing depolarization ofthe right and left ventricles, and optimizing the AV sequence on bothsides of the heart. In the patent literature, U.S. Pat. No. 4,928,688 isrepresentative of a system for simultaneous left ventricular (LV) andright ventricular (RV) pacing; natural ventricular depolarizations aresensed in both chambers, if one chamber contracts but the other one doesnot within a window of up to 5-10 ms, then the non-contractingventricular chamber is paced.

In addition to the above-mentioned disclosures concerning the advantagesof substantially simultaneous or synchronous pacing of the twoventricles, it is known that there is an advantage to synchronous pacingof the left atrium and the right atrium for patients with IAB,inter-atrial block. In a normal heart, atrial activation initiates withthe SA node, located in the right atrial wall. In a patient with IAB,the activation is slow being transferred over to the left atrium, and asa result the left atrium may be triggered to contract up to 90 ms laterthan the right atrium. It can be seen that if contractions in the leftventricle and the right ventricle are about the same time, then left AVsynchrony is way off, with the left ventricle not having adequate timeto fill up. The advantage of synchronous pacing of the two atria forpatients with IAB is disclosed at AHA 1991, Abstract from 64thScientific Sessions, “Simultaneous Dual Atrium Pacing in High DegreeInter-Atrial Blocks: Hemodynamic Results,” Daubert et al., No. 1804.Further, it is known that patients with IAB are susceptible toretrograde activation of the left atrium, with resulting atrialtachycardia. Atrial resynchronization through pacing of the atria can beeffective in treating the situation. PACE, Vol. 14, April 1991, Part II,p. 648, “Prevention of Atrial Tachyarrythmias Related to Inter-AtrialBlock By Permanent Atrial Resynchronization,” Mabo et al., No. 122. Forpatients with this condition, a criterion for pacing is to deliver aleft atrial stimulus before the natural depolarization arrives in theleft atrium.

In view of the published literature, it is observed that in CHF patientsimproved pump function can be achieved by increasing the filling time ofthe left ventricle, i.e., improving the left AV delay, and specificallythe left heart mechanical AV delay (MAVD); decreasing mitral valveregurgitation, (back flow of blood through the nearly closed valve) bytriggering contraction of the left ventricle when and as it becomesfilled; and normalizing the left ventricular activation pattern, i.e.,the time sequence of left atrial contraction relative to right atrialcontraction. More specifically, for a cardiac pacing system used fortreating a CHF patient, the aim is to capture the left atrium; optimizethe left AV delay so as to properly fill the left ventricle and providea more normal AV delay; and activate the left ventricle as much aspossible in accordance with the natural propagation path of a healthyleft heart. Particularly, left ventricular timing with respect to theleft atrial contraction is crucial for improving cardiac output. Themechanical closure point of the left, or mitral valve, is a crucialmoment which needs to be adjusted by programming of the left AV delay.Correct programming of this variable is key for optimizing the fillingof the left ventricle, and optimizing ejection fraction, or cardiacoutput (CO).

An observation which is important to this invention is that the exacttiming of mechanical events are important for properly controllingpacing so as to optimize left ventricular output. Specifically, it isknown that actual contraction of one ventricular chamber before theother has the effect of moving the septum so as to impair fullcontraction in the later activated chamber. Thus, while concurrent orsimultaneous pacing of the left and right ventricle may achieve asignificant improvement for CHF patients, it is an aim of this inventionto provide for pacing of the two ventricles in such a manner that theactual mechanical contraction of the left ventricle, with the consequentclosing of the valve, occurs in a desired time relationship with respectto the mechanical contraction of the right ventricle and closing of theright value. For example, if conduction paths in the left ventricle areimpaired, delivering a pacing stimulus to the left ventricle atprecisely the same time as to the right ventricle may nonetheless resultin left ventricular contraction being slightly delayed with respect tothe right ventricular contraction. As a consequence, it is important forthis invention to provide a technique for measurement of mechanicalevents, such as a mechanical closure point of each of the ventricles, soas to be able to accurately program the sequence of pacing to achievethe desired dual ventricular pacing which optimizes ejection fraction,or cardiac output, for the individual patient.

In view of the above-noted importance of measuring mechanical events,such as mitral or tricuspid valve closure, and the importance ofmeasuring cardiac output, it is necessary for the pacing system of thisinvention to employ sensors which can provide this information. It isknown to use impedance sensors in pacing systems, for obtaininginformation concerning cardiac function. For example, reference is madeto U.S. Pat. No. 5,501,702, incorporated herein by reference, whichdiscloses making impedance measurements from different electrodecombinations. In such system, a plurality of pace/sense electrodes aredisposed at respective locations, and different impedance measurementsare made on a time/multiplexing basis. As set forth in the referencedpatent, the measurement of the impedance present between two or moresensing locations is referred to “rheography.” A rheographic, orimpedance measurement involves delivering a constant current pulsebetween two “source” electrodes, such that the current is conductedthrough some region of the patient's tissue, and then measuring thevoltage differential between two “recording” electrodes to determine theimpedance therebetween, the voltage differential arising from theconduction of the current pulse through the tissue or fluid between thetwo recording electrodes. The referenced patent discloses usingrheography for measuring changes in the patient's thoracic cavity;respiration rate; pre-ejection interval; stroke volume; and heart tissuecontractility. It is also known to use this technique of four pointimpedance measurements, applied thoracically, for measuring smallimpedance changes during the cardiac cycle, and extracting the firsttime derivative of the impedance change, dZ/dt. It has been found that asubstantially linear relation exists between peak dZ/dt and peak cardiacejection rate, providing the basis for obtaining a measure of cardiacoutput. See also U.S. Pat. No. 4,303,075, disclosing a system formeasuring impedance between a pair of electrodes connected to or inproximity with the heart, and processing the variations of sensedimpedance to develop a measure of stroke volume. The AV delay is thenadjusted in an effort to maximize the stroke volume.

Given the demonstrated feasibility of four-chamber cardiac pacing, andthe availability of techniques for sensing natural cardiac signals andmechanical events, there nonetheless remains a need for developing asystem which is adapted to the cardiac condition of a patient with CHF,so as to provide pacing sequences which are tuned for improving cardiacoutput, and in particular for improving left heart function. It is apremise of this invention that such a system is founded upon accuratemeasurements of mechanical events, and use of the timing of suchmechanical events to control and program pacing sequences.

SUMMARY OF THE INVENTION

It is an overall object of this invention to provide a pacing system formultiple chamber pacing, and in particular, for pacing the patient'sleft heart in coordination with the electrical activation and mechanicalevents of the patient's right heart, so as to optimize left heartoutput. In accordance with this invention, there is provided afour-chamber pacing system, having leads carrying electrodes positionedfor pacing and sensing in or on each of the four cardiac chambers.Additionally, the leads are connected to obtain impedance measurementsfrom which accurate timing signals are obtained reflecting mechanicalactions, e.g., valve closures, so that accurate timing information isavailable for controlling electrical activation and resultant mechanicalresponses for the respective different chambers. The impedance ormechanical sensing determinations are preferably made by multi-plexingthrough fast switching networks to obtain the desired impedancemeasurements in different chambers.

In a preferred embodiment, control of four-chamber pacing, and inparticular left heart pacing, is based primarily upon initial detectionof a spontaneous signal in the right atrium, and upon sensing ofmechanical contraction of the right and left ventricles. In a heart withnormal right heart function, the right mechanical AV delay is monitoredto provide the timing between the initial sensing of right atrialactivation (P-wave) and right ventricular mechanical contraction. Theleft heart is controlled to provide pacing which results in leftventricular mechanical contraction in a desired time relation to theright mechanical contraction; e.g., either simultaneous or justpreceding the right mechanical contraction; cardiac output is monitoredthrough impedance measurements, and left ventricular pacing is timed tomaximize cardiac output. In patients with intra-atrial block, the leftatrium is paced in advance of spontaneous depolarization, and the leftAV delay is adjusted so that the mechanical contractions of the leftventricle are timed for optimized cardiac output from the leftventricle.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a system in accordance with thisinvention, whereby four bipolar leads are provided, the leads beingshown carrying bipolar electrodes positioned in each of the respectivecardiac chambers.

FIG. 2A is a block diagram of a four channel pacing system in accordancewith this invention, for pacing and sensing in each ventricle, and forobtaining impedance signals from the left heart and the right heart;FIG. 2B is a schematic representation of an arrangement in accordancewith this invention for detecting left ventricular impedance fordetermination of cardiac output.

FIG. 3 is a block diagram of a four-chamber pacemaker with the abilityto time multiplex impedance measurements, in accordance with thisinvention.

FIG. 4 is a block diagram of a system implementation in accordance withan embodiment of this invention for controlling left ventricular pacingin a patient with LBBB.

FIG. 5 is a flow diagram for a system implementation in accordance withan embodiment of this invention, for controlling left atrial andventricular pacing in a patient with IAB.

FIG. 6 is a flow diagram of a routine in accordance with this inventionfor optimizing bi-ventricular pacing to provide maximum cardiac output.

FIG. 7 is a block schematic of a pacemaker in accordance with thisinvention for providing selectable four-chamber pacing and cardiacsignal sensing, as well as impedance sensing between selectedcombinations of the four heart chambers.

FIG. 8A is a flow diagram of a process using inter-atrial orinter-ventricular impedance measurements for determination of existenceof arrhythmias; FIG. 8B is a flow diagram illustrating a procedure forobtaining atrio-ventricular cross-impedance measurements for obtainingindications of heart failure.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the description of the preferred embodiments, and with reference tothe drawings, the following designations are used:

DRAWING DESIGNATION DEFINITION RA right atrium RV right ventricle RH RAand RV LH LA and LV LA left atrium LV left ventricle LAS left atrialsense RAS right atrial sense LAP left atrial pace pulse LVP leftventricular pace pulse RMAVD time interval between RAS and mechanicalcontraction of RV (as measured, e.g., by valve closure) LMAVD timeinterval between LAS or LAP and mechanical contraction of LV RAVD timeinterval between RAS and QRS in RV LAVD time interval between LAS orLAP, and QRS in LV

Referring now to FIG. 1, there is shown a schematic representation of afour-chamber pacing system, illustrating four pacing leads providingbipolar electrodes positioned for pacing and sensing in each of therespective heart chambers, and also for impedance measurements. Pacinglead 38 is positioned conventionally such that its distal end is in theright ventricular apex position. It carries bipolar electrodes 38 a and38 b adapted for pacing and sensing; additionally, these electrodes canalso be used for impedance sensing as discussed below. Likewise, atriallead 36 is positioned so that its distal end is positioned within theright atrium, with bipolar electrodes 36 a, 36 b. Lead 34 is passedthrough the right atrium, so that its distal end is positioned in thecoronary sinus for pacing, sensing and impedance detection throughelectrodes 34 a, b, as shown. Likewise, lead 32 is positioned via thecoronary sinus a cardiac vein, e.g., the middle or great cardiac vein,so that distal electrodes 32 a and 32 b are positioned approximately asshown for pacing, sensing and impedance detection with respect to theleft ventricle. The pacing leads are connected to pacemaker 30 in aconventional manner. It is to be understood that each of the four leadscan have one or more additional electrodes; however, by using timemultiplexing techniques as discussed below and in the referenced U.S.Pat. No. 5,501,702, pacing, sensing and impedance detection can beaccomplished with only two electrodes per lead. Referring now to FIGS.2A and 2B, there is shown a simplified block diagram of a four channelpacemaker in accordance with this invention, having the additionalcapability of impedance detection to sense valve movement of the leftand right ventricles. Although discussion of FIG. 2A is presented withrespect to valve movement, it is to be understood that the impedancedetection scheme may be altered to detect other mechanical events, suchas ventricular wall contraction, in a known manner.

The system of FIG. 2A contains, in the pacemaker, a central processingblock 40, indicated as including timing circuitry and a microprocessor,for carrying out logical steps in analyzing received signals,determining when pace pulses should be initiated, etc., in a well knownfashion. Referring to the upper left-hand corner of the block diagram,there is shown signal amplifier circuitry 41, for receiving a signalfrom the right atrium. Electrode 36 a is illustrated as providing aninput, it being understood that the second input is received either frombipolar electrode 36 b, or via an indifferent electrode (the pacemakercan) in the event of unipolar sensing. Likewise, a pulse generator 42,acting under control of block 40, generates right atrial pace pulses fordelivery to electrode 36 a and either electrode 36 b or system ground.In a similar manner, right ventricular pace pulses (RVP) are generatedat output stage 43 and connected to electrode 38 a, and sensed rightventricular signals are inputted to sense circuitry 44, the output ofwhich is delivered to control block 40. Also illustrated is impedancedetector 45, which receives inputs from electrodes 36 a, 38 a, fordelivering information corresponding to right heart valve closure, whichtiming information is inputted into control block 40. Thus, the systemenables pacing and sensing in each chamber, as well as impedancedetection to provide an indication of the timing of right heart valveclosure, which represents the time of mechanical contraction of theright valve.

Still referring to FIG. 2A, there are shown complementary circuitcomponents for the left atrium and the left ventricle. Output generatorstage 47, under control of block 40, delivers left atrial pace pulses(LAP) to stimulate the left atrium through electrode 34 a and eitherelectrode 34 b or system ground. Inputs from the left atrial lead areconnected through input circuitry 46, the output of which is connectedthrough to control block 40. In a similar fashion, output stage 48,under control of block 40, provides left ventricular stimulus pacepulses (LVP) which are delivered across electrode 32 a and eitherelectrode 32 b or system ground; and left ventricular signals are sensedfrom lead 32 and inputted to input circuit 49, which provides an outputto block 40 indicative of left ventricular signals. Also, dual inputsfrom the left atrial electrode 34 a and left ventricular electrode 32 aare inputted into left heart impedance detector 50, which providestiming pulses to block 40 indicative of the timing of left heart(mitral) valve closure. With this arrangement, the pacemaker has thebasic timing and cardiac signal information required to program deliveryof pace pulses to respective heart chambers in accordance with thisinvention. Block 40 contains current generators for use in impedancedetection; microprocessor or other logic and timing circuitry; andsuitable memory for storing data and control routines.

Referring to FIG. 2B, there is shown a diagrammatic sketch of anarrangement for detecting left ventricular impedance change, which isprocessed in block 40 to obtain an indication of cardiac output. Asshown, a current source 52 provides a constant current source acrosselectrode 53 in the right atrium, which suitably can be electrode 36 a;and right ventricular electrode 54, which suitably can be electrode 38a. The current source can be pulsed, or it can be multiplexed in amanner as discussed below. Impedance sensors 57 and 58 provide signalsrepresentative of impedance changes therebetween, the impedance being afunction of blood volume and valve closure, as discussed above. Theoutputs from electrodes 57, 58 is connected across impedance detector56, which represents the microprocessor and/or other processingcircuitry in block 40 for analyzing the impedance changes and making adetermination of cardiac output. As is known, a measure of cardiacoutput can be obtained by extracting the first time derivative ofcyclical impedance changes, dz/dt; a linear relationship exists betweenpeak dz/dt and peak ejection rate.

Referring now to FIG. 3, there is shown a block diagram of a pacemaker30 in accordance with a preferred embodiment of this invention, formultiplexing connections to electrodes so as to provide for pacing andsensing in any one of the four cardiac chambers, as well as forimpedance determinations between respective different lead electrodes.Reference is made U.S. Pat. No. 5,501,702, incorporated herein byreference, for a full discussion of this circuit, and in particular themultiplexing arrangement carried out by switch matrices 68, 70. Thepacemaker 30 operates under control of circuitry 62, which may include amicroprocessor or custom integrated circuitry, as well as associatedmemory, in a manner well known in the pacemaker art. Circuitry 62provides for processing of data, and generation of timing signals asrequired. Control circuitry 62 is coupled to pace/sense circuitry 64,for processing of signals indicating the detection of electrical cardiacevents, e.g., P-waves, R-waves, etc. sensed from conductors whichconnect electrically to electrodes 32 a-38 b, as shown. Theaforementioned leads are also coupled to a first switch matrix 68 and asecond switch matrix 70. Matrix 68 establishes a selectableinterconnection between specific ones of the electrodes of leads 32, 34,36 and 38, and the current source 72, is controlled by circuit 62. In asimilar manner, switch matrix 70 establishes a selectableinterconnection between lead conductors corresponding to selectedelectrodes, and impedance detection circuit 74, for the purpose ofselecting impedance measurements.

Still referring to FIG. 3, current source 72 receives control signals online 73 from circuitry 62, and is responsive thereto for deliveringconstant current rheography pulses onto lead conductors selected byswitching matrix 68, which in turn is switched by signals on bus 83.Impedance detection circuit 74 is adapted to monitor the voltage betweena selected pair of electrodes which pair is selectably coupled byoperation of switch matrix 70 which in turn is switched by signals onbus 80. In this manner, circuit 74 determines the voltage, and hence theimpedance, existing between two selected electrodes. The output ofcircuitry 74 is connected through A/D converter 76 to control circuitry62, for processing of the impedance signals and determination of theoccurrence of mechanical events, such as left or right heart valveclosure. The control of switch matrix 68 through signals on bus 78, andthe control of switch matrix 70 through signals on bus 80, provides formultiplexing of different impedance signals.

It is to be understood that in the system arrangement of FIG. 3,pace/sense circuitry 64 may include separate stimulus pulse outputstages for each channel, i.e., each of the four-chambers, each of whichoutput stages is particularly adapted for generating signals of theprogrammed signal strength. Likewise, the sense circuitry of block 64may contain a separate sense amplifier and processor circuitry forsensed signals from each chamber, such that sensing of respective waveportions, such as the P-wave, R-wave, T-wave, etc. from the RH and theLH, can be optimized. The pulse generator circuits and sense circuits asused herein are well known in the pacemaker art. In addition, otherfunctions may be carried out by the control circuitry including standardpacemaker functions such as compiling of diagnostic data, modeswitching, etc.

Referring now to FIG. 4, there is shown a logic control flow diagram forcontrolling the system of this invention to pace a patient with LBBB.The assumption is that the RH is normal, and that sinus signals from theSA node are being normally conducted to the LA; but that the LBBB ismanifested by slow conduction to the LV, such that the LV does notcontract when it should. As a consequence, there is mitralregurgitation, or backflow of blood through the valve because the LVdoes not contract when it is filled from the LA; and the contraction ofthe LV, when it occurs, is later than that of the RV, furthercontributing to decrease of LH output.

As seen at 101, the pacemaker monitors the RH, and gets a measure ofRMAV. This is done by sensing right valve closure through RH impedancemeasurement, and timing the delay from the atrial depolarization (RAS)to valve closure. Then, at 102, the pacemaker is controlled to pace LVwith an LAVD such that LMAVD is about equal to RMAVD. During this step,impedance measurements are made in the LV, and a measure of LMAVD isobtained. Based on this determination, the value of LAVD is adjusted tosubstantially match LMAVD with RMAVD. Note that normal conductionthrough the LV takes on the order of 50-60 ms, so it is expected thatthe LV should be paced in advance of the occurrence of RV valve closure,so that LV valve closure occurs at about the same time as, or even a bitbefore RV valve closure. Causing the LV to contract just before the RVmight provide an increase of LH output which outweighs the smallresulting RV dysfunction due to the septum being pulled toward the LVfirst. Thus, the timing of delivery of each LVP is adjusted to set LMAVDapproximately equal to RMAVD. Then, at 104, the value of LAVD is furtheradjusted, while R and L valve closure is monitored, and LMAVD isadjusted relative to RMAVD. This adjustment, or variation of LMAVD, maybe made by incrementally changing LAVD each cycle, or each n cycles, toscan relative to the value of RMAVD. Cardiac output is obtained througha left heart impedance measurement, and appropriate signal processing,for each setting of the differential between the right and left valveclosures, and respective values of CO and LMAVD are stored at 105. Thehighest, or maximum value of cardiac output is determined, and LAVD isset so that the resultant MLAVD is at the differential compared to RMAVDto yield the highest cardiac output. In this manner, the timing of leftventricular pace pulses is set to produce substantial bi-ventricularmechanical synchronization for the greatest cardiac output. Thedetermined value of LAVD and the corresponding LV-RV difference isstored.

Still referring to FIG. 4, at 106 the pacemaker proceeds to pace the LVwith this established value of LAVD, providing mechanicalsynchronization. Of course, if the natural sinus rate varies, thepacemaker wants to follow; if the spontaneous RAVD varies, but the LAVDdoesn't follow the change, the mechanical synchronization will be lost.Accordingly, at 107 the pacer monitors the natural sinus rate, or atrialpacing rate, and determines if there has been a significant change inatrial rate. If yes, at 109, the pacer adjusts LAVD accordingly tomaintain mechanical sync for optimum output. Although not shown, thepacemaker can periodically go back to block 101 to re-determine thedesired value of LAVD.

Referring now to FIG. 5, there is shown a flow diagram for pacing of apatient with IAB; such patient may have LBBB as well. Here, it isnecessary to take control of the LA by pacing before atrialdepolarization is conducted (late) to the LA. At 110, the pacemakermonitors the pattern of LA depolarization relative to RA depolarization,i.e., it determines the inter-atrial delay. At 111, it is determinedwhether the LA should be paced, based on the atrial depolarizationpattern. If yes, the pacemaker sets an RA-LA delay at 112, whichcorresponds to a healthy heart, and which enables capture of the LA. At114, the value of RMAVD is obtained, as was described in connection withFIG. 4. Then, at 116, LAVD is determined for a first setting ofmechanical sync; this can be done by setting LAVD to produce LVcontraction at the same time as RV contraction (valve closure), orearlier by a small time increment. Then, LAVD is varied, as shown at117, and LMAVD and CO are determined corresponding to each value ofLAVD. The value of LAVD is set to that value which corresponds tomaximum cardiac output, and this value and the LV-RV mechanicalrelation, or mechanical sync value is stored for the chosen LAVD. At118, the pacemaker paces LA and LV, in accord with the values that havebeen determined. In the event of significant change in atrial rate, LAVDis adjusted to compensate for the rate change, and to substantiallymaintain the LV-RV mechanical relationship previously found tocorrespond to maximum cardiac output, as shown at 120, 121. Although notshown, in the event of large changes in the sinus rate, or passage of apredetermined amount of time, determination of inter-atrial delay andLAVD can be repeated automatically.

Referring now to FIG. 6, there is shown a simplified flow diagram for aprocedure in accordance with this invention for carrying outbi-ventricular pacing so as to maximize cardiac output (CO). Thisroutine is adapted for patients who need right ventricular pacing, andwho can benefit from synchronous left ventricular pacing as well. Inthis example, it is assumed that atrial pacing is not required, but ifthe patient requires atrial pacing, the routine can be adaptedappropriately.

At block 130, a common value of AV delay (AVD) is first set. At block132, both the left ventricle and the right ventricle are paced,initially with the previously set value of AVD, but then with a varyingAVD. As AVD is varied, or scanned relative to the initial setting, thepacemaker makes determinations of cardiac output by processing impedancesignals from the left heart, or left ventricle, in the manner discussedabove. Values of CO are stored together with the different values ofAVD, and the optimum value of a common AVD is determined correspondingto maximum CO. Then, at block 134, the value of LAVD is varied relativeto RAVD, such that the left pacing pulse is delivered at differing timesfrom the right pacing pulse. It is to be remembered, as discussed above,that for maximum cardiac output, it may be desirable to pace the leftventricle shortly before the right ventricle, and this step is asearching step to determine the time relationship between the twoventricular pace pulses which results in the best cardiac output. CO isdetermined as the ventricular sync relationship is varied, and thecorresponding optimum LAVD is determined. When this has been obtained,the routine goes to block 136 and paces the patient at the determinedvalues of LAVD and RAVD. Periodically, as indicated at 138, thepacemaker can determine whether a test is desired. If yes, the routinebranches back to 130, to loop through the test and redetermine theoptimum values of LAVD and RAVD. It is to be noted that the steps ofblocks 132 and 134 can be done in a reverse sequence, i.e., step 134first and then step 132.

Referring now to FIG. 7, there is shown an alternate block diagram ofcomponent portions of a pacemaker in accordance with this invention, forproviding maximum flexibility in terms of pacing, cardiac signal sensingand impedance sensing. At least two electrodes are positioned in orproximate to each heart chamber, in the manner as discussed above inconnection with FIG. 1, and connected in turn to block 150. As indicatedin FIG. 7, block 150 is an output/input switch matrix, and interconnectswith block 152 in the manner as described in FIG. 3. Thus, block 152provides pacing pulses which can be connected through matrix 150 to eachof the four chambers, and has sense amplifier circuitry for sensingsignals from each of the four chambers. Block 150 further provides amultiplex switch array for switching a current source across selectedpairs of the eight electrodes for impedance measuring purposes, again inaccordance with the discussion of FIG. 3. The sensed impedance signalsare suitably transferred from array 150 to digital signal processingcircuitry 161, which is part of block 152. Block 152 is in two-wayconnection with the timing modules shown in block 154, for timinggeneration of pace pulses, current source pulses, and the generation ofsensing windows. Blocks 150, 152 and 154 are further inter-connected bycontrol bus 163. Data is transferred between signal processing block 170and block 154 across data bus 157. Block 154 in turn is inter-connectedwith microprocessor 156, through household bus 151, data bus 153 andcontrol bus 154. By this arrangement, impedance sensing can be carriedout across any combination of the four heart chambers, e.g., rightatrium vs. left atrium; right ventricle vs. left ventricle; right atriumvs. left ventricle; and left atrium vs. right ventricle. Impedancemeasurements between these combinations of chambers can be carried outin accordance with this invention, for purposes of analyzing andconfirming arrhythmias, including fibrillation. Further, changes inconduction patterns, as seen in the morphology of such impedancemeasurements, can be monitored and processed for making determinationsof progression of heart failure. Thus, cross-measurements of RA-LV andLA-RV can be useful in obtaining histories to determine changesindicating progression of heart failure.

Referring now to FIG. 8A, at block 160, the pacemaker first obtainsimpedance measurements either between LA and RA, or between LV and RV.These impedance values are processed at 162, and at 164 a determinationis made as to whether the atrial or ventricular rhythms are regular ornon-physiological. This determination can be made, for example, simplyby sensing differences over time and comparing such differences topredetermined criteria. If a rhythm is determined not to be regular,then a determination of arrhythmia is made at 166. A suitable responseis made at 168. Referring to FIG. 8B, at block 170 the pacemaker obtainscross-measurements of impedances, e.g., between RA and LV or between LAand RV. These measurements are stored and processed as indicated at 172,and evaluated at 174 to determined whether they indicate HF orprogression toward HF. If yes, an appropriate response can be made,illustrated at 176, e.g., providing a warning which can be retrieved byan external programmer.

The scope of the invention extends to other conditions of CHF, inaddition to the ones illustrated here. In each case, the condition ofthe patient must be responded to on an individual basis. However, inaccordance with this invention, the system response includes adetermination of mechanical events, e.g., valve closure, preferably ineach side of the heart, and programming of pacing escape intervals basedon consideration of the mechanical events and a determination ofvariations of cardiac output with variations of LAVD and/or mechanicalventricular synchronization. The system of this invention can be used inan implanted pacemaker system; or, the system procedures can be carriedout with an external system, for determination of optimum programming ofa pacemaker which is to be implanted or re-programmed.

What is claimed is:
 1. A pacing system for providing pacing of a patient's left heart, comprising: first means for obtaining indications of mechanical contractions of the right ventricle; left ventricular pacing means for pacing the left ventricle; and LV control means for controlling the timing of said left ventricular pacing relative to indicated right ventricular mechanical contractions.
 2. The pacing system as described in claim 1, comprising second means for obtaining indications of mechanical contractions of the left ventricle, and wherein said LV control means has means for controlling the timing of said left ventricular pacing so as to provide substantially synchronous left and right ventricular mechanical contractions.
 3. The pacing system as described in claim 2, comprising left atrial pacing means for pacing the patient's left atrium; left AV control means for controlling the left AV delay between pacing the left atrium and the left ventricle, cardiac output means for measuring left heart output as a function of said left AV delay, and wherein said left AV control means further comprises maximizing means for adjusting said left AV delay to maximize left cardiac output.
 4. The pacing system as described in claim 3, comprising means for sensing sinus signals, and left atrial timing means for timing delivery of left atrial pacing pulses relative to said sinus signals.
 5. The pacing system as described in claim 1, wherein said LV control means has means for delivering a left ventricular pacing pulse just before the expected time of the next right ventricular mechanical contraction.
 6. The system as described in claim 1, wherein said first means comprises an impedance measuring circuit for obtaining an impedance signal representative of impedance between the patient's right atrium and right ventricle, and processing means for processing said impedance signal to determine the timing of right heart valve closures.
 7. The system as described in claim 1, comprising second impedance means for obtaining a left impedance signal representative of impedance change over the patient's left heart, and second processing means for processing said left impedance signal to obtain a measure of left heart output.
 8. The system as described in claim 7, comprising third processing means for processing said left impedance signal to obtain filling signals indicative of the filling of the left ventricle, and wherein said LV control means comprises means for controlling timing of said left ventricular pacing signals as a function of said filling signals.
 9. The system as described in claim 1, further comprising means for obtaining indications of left ventricular mechanical contractions, and wherein said LV control means comprises mechanical sync means for controlling said left ventricular pacing to achieve mechanical synchrony of said left and right mechanical contractions.
 10. The system as described in claim 9, wherein said mechanical sync means comprises adjusting means for adjusting the timing of aid left ventricular pacing so as to maximize left heart output.
 11. A four-chamber pacing system for providing pacing of a patient's left heart to improve cardiac output, comprising: RV means for determining the timing of right ventricular mechanical contractions; LV means for determining the timing of left ventricular mechanical contractions; and pacing sync means for pacing the patient's left ventricle; and control means for controlling said pacing means so as to substantially synchronize said left and right mechanical contractions.
 12. The four-chamber pacing system as described in claim 11 comprising: LA means for determining the timing of left atrial depolarization; CO means for measuring cardiac output from the patient's left heart; and wherein said control sync means comprises LA VO means for controlling said pacing means to deliver pacing pulses to said patient's left ventricle at a left atrio-ventricular delay following left atrial depolarizations, and adjusting means for adjusting said left atrio-ventricular delay to correspond to maximum measured cardiac output.
 13. A four chamber pacing system, having electrodes positioned in each of a patient's four heart chambers, comprising: impedance means for obtaining impedance measurements between a selected pair of said four chambers; processing means for processing said impedance measurements, and determining changes in said measurements over a period of time; and determining means for determining whether any said change occurs which indicates a physically abnormal heart condition.
 14. The system as described in claim 13, wherein said determining means determines whether any such change occurs which is indicative of an arrhythmia.
 15. The system as described in claim 13, wherein said determining means comprises means for determining whether said any such change occurs which indicates a heart failure condition.
 16. The system as described in claim 13, comprising programmable selection means for selecting impedance measurements between any two of said four heart chambers. 